What is the typical dosing regimen for testosterone replacement therapy in men with hypogonadism based on laboratory results?

Testosterone Replacement Therapy Dosing for Men with Hypogonadism

For men with confirmed hypogonadism, the recommended testosterone replacement therapy (TRT) dosing regimen is 200 mg every 2 weeks or 100 mg weekly via intramuscular injection, targeting serum testosterone levels between 450-600 ng/dL. 1, 2

Diagnosis and Initial Assessment

• Confirm hypogonadism with morning serum testosterone levels <300-350 ng/dL on two separate occasions before 10 AM 1
• Assess free testosterone in obese patients due to potential SHBG alterations 1
• Evaluate for primary vs. secondary hypogonadism by measuring FSH/LH levels 1

Dosing Options

Intramuscular (IM) Testosterone Cypionate

• Initial dose: 50-400 mg every 2-4 weeks 2
• Most effective regimens based on evidence:
  • 200 mg every 2 weeks (preferred for balance of efficacy and convenience) 3
  • 100 mg weekly (provides most stable testosterone levels) 3, 4
  • 300 mg every 3 weeks (acceptable alternative) 3

Subcutaneous Testosterone

• Alternative option: 75-100 mg weekly subcutaneous testosterone enanthate 5
• Advantages: less painful, more stable testosterone levels, lower risk of hematocrit elevation and estradiol increases compared to IM 4, 6, 5

Monitoring and Dose Adjustment

1. Check testosterone levels 4-6 weeks after initiation 1
2. Target testosterone levels: 450-600 ng/dL 1
3. Monitor:
   • Testosterone levels every 3-6 months 1
   • Hematocrit/hemoglobin (discontinue if hematocrit >54%) 7, 1
   • PSA levels 1
   • Blood pressure 1
   • Symptom improvement 1

Dose Adjustment Algorithm

1. If testosterone <300 ng/dL: Increase dose by 50 mg
2. If testosterone >600 ng/dL: Decrease dose by 50 mg
3. If hematocrit >54%: Reduce dose, consider therapeutic phlebotomy, or switch to transdermal formulation 7, 1

Formulation Considerations

• IM injections are associated with higher risk of erythrocytosis (43.8%) compared to transdermal preparations (5.5-15.4%) 7
• Higher doses correlate with increased risk of erythrocytosis: 2.8% at 5 mg/day, 11.3% at 50 mg/day, and 17.9% at 100 mg/day with gel preparations 7
• Subcutaneous administration shows lower post-therapy hematocrit and estradiol levels compared to IM testosterone cypionate 4

Common Pitfalls to Avoid

• Diagnosing hypogonadism based on a single testosterone measurement 1
• Failing to measure free testosterone in obese patients 1
• Not monitoring for adverse effects, particularly hematocrit elevation 7, 1
• Using testosterone for "age-related hypogonadism" without structural or genetic etiology 1
• Using testosterone in men desiring fertility (use SERMs, AIs, or hCG instead) 1

Contraindications

• Prostate cancer
• Male breast cancer
• Desire for fertility in near future
• Severe obstructive sleep apnea
• Uncontrolled congestive heart failure
• Hematocrit >54% 1

The evidence supports that proper dosing and monitoring of testosterone replacement therapy can provide significant improvements in sexual function, quality of life, energy levels, and depressive symptoms in men with confirmed hypogonadism 1.